The objective of this proposal is to better define the role of the activated macrophage in host resistance to cancer and intracellular infection. We plan to evaluate the in vitro cytotoxic activity of human macrophages by applying data we have obtained and techniques we have developed in completed animal model studies to help better understand the biology of nonspecific resistance in man. The in vitro cytotoxicity test we developed using mouse peritoneal macrophages and mouse target cells will be adapted for use, employing human blood monocyte-derived macrophages and human target cells. The in vitro cytotoxic activity of macrophages from patients with cancer will be tested with autologous and allogeneic tumor cells. This should enable us to relate the role of the macrophage to clinical host resistance in patients with cancer. The effect of various treatment regimens--nonspecific immunotherapy, chemotherapy, radiotherapy, or surgery--on the cytotoxicity of the patient's macrophages will be investigated. In addition, to better define nonspecific factors of host resistance and relate them to specific immune mechanisms, a profile of immunologic parameters will be measured on patients whose macrophage function is studied in vitro. All studies are designed to lead to a better definition of nonspecific effector mechanisms in the homeostatic control of carcinogenesis and tumor growth. BIBLIOGRAPHIC REFERENCES: Hibbs, J. B., Jr. 1975. Activated Macrophages as Cytotoxic Effector Cells. I. Inhibition of Specific and Nonspecific Tumor Resistance by Trypan Blue. Transplantation, 19:77-81. Hibbs, J.B., Jr. 1975. Activated Macrophages as Cytotoxic Effector Cells. II. Requirement for Local Persistence of Inducing Antigen. Transplantation, 19:81-87.